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Clinical Trials Fighting Blindness

Establishing Proof

Some Fifty Years Ago a Baby-Blinding Epidemic Confounded Experts -- Until a Pioneering Study Conclusively Tied Cause and Effect, and Enshrined Clinical Trials in Medical Practice

By David Brown

Washington Post Staff Writer
Tuesday, April 19, 2005; Page HE01

Marc Maurer was born on June 3, 1951, in Des Moines, the second child of a traveling salesman and a housewife. He was two months premature. As is often the case with babies born very early, his lungs were underdeveloped. He spent two months in the hospital. During the first, supplemental oxygen was pumped into his incubator continuously.

In the same city three months earlier, Patricia Schaaf was born. Her father was a plumber, her mother was a school cook. Their first child, Patricia was 3 pounds, 10 ounces at birth and two months premature. She, too, got oxygen for at least a month.

Marc Maurer, President of the National Federation of the Blind, with his wife Patricia. Both were born prematurely and both became blind from oxygen given to them in their first weeks of life.
(Michael Williamson - The Washington Post)

Maurer is president of the National Federation of the Blind, and his wife -- the former Patricia Schaaf -- is its director of community relations. They work in South Baltimore in a refurbished factory that is the headquarters of the 50,000-member advocacy organization. Marc Maurer, a lawyer by training, has a spacious corner office overlooking the Patapsco River, which he cannot see.

The Maurers were part of an epidemic that began in the early 1940s and peaked in 1951, the year of their birth. They were blinded by high concentrations of oxygen, which was routinely given to premature infants in the United States during and after World War II. It took 15 years to discover the link between oxygen and blindness -- 15 years in which a mysterious disease haunted America's best hospitals.

This tragic outbreak was not the first time a medical treatment thought to be beneficial was shown to cause harm. Nor would it be the last.

In recent years, hormone replacement therapy taken by millions of women turned out to cause heart attacks, not prevent them. Vitamin A supplements don't lower the risk of lung cancer, as many smokers once thought; it may increase it. Antidepressants relieve depression in some teenagers but appear to drive a small number toward suicide, depression's tragic endpoint. Three years ago the pain reliever Vioxx was the 15th most commonly prescribed drug in the United States, with $1.8 billion in annual sales. Today, some experts believe it may have contributed to as many as 160,000 heart attacks and strokes since its arrival in 1999.

The story of oxygen and blindness is a distant mirror of these therapeutic surprises. But it is much more as well.

Of all the elements on the periodic table, oxygen is the one that seems most to symbolize life and health itself. Could extra oxygen be dangerous to tiny babies struggling to survive? It seemed inconceivable!

But it was true. Two doctors proved it more than a half-century ago in a clinical experiment run in the wards of a hospital in Washington. The medical world didn't believe them, at least not enough to change routine practice. So a second, bigger experiment was conducted at more than a dozen American hospitals.

Fifty years ago this summer, the preliminary results of that trial were published. They changed medical history. Almost overnight, physicians stopped automatically giving supplemental oxygen to preemies, ending the epidemic of retrolental fibroplasia (RLF), as the disease was called then. (It is now known as retinopathy of prematurity.)

But the study's results did something else equally important and historic. They convinced many American physicians of the usefulness of randomized controlled trials, which had been "invented" less than 10 years earlier in Britain. Not least, the study taught doctors they couldn't assume that what seemed like a good idea -- extra oxygen -- would necessarily lead to a good outcome.

"Doctors have to approach their patients, and what they think they know, with a certain amount of humility," said Steven Goodman, a physician at Johns Hopkins University's Bloomberg School of Public Health and editor of the journal Clinical Trials. "This is one of the trials that taught us humility."

The events that culminated 50 years ago is also a story of self-reliance, doggedness and even heroism on the part of the blind survivors of RLF and the two doctors who first proved the disease's cause. Those doctors, as it happens, are still alive.

Arnall Patz went on to become the chairman of ophthalmology at Johns Hopkins University School of Medicine . Now 84 and officially retired, he lives in Baltimore and still works part of nearly every day on some medical project. Last spring, President Bush awarded him the Presidential Medal of Freedom for a lifetime of scientific discovery that began with the oxygen experiment at Gallinger Municipal Hospital, the predecessor of D.C. General. His long-ago collaborator in that work is Leroy E. Hoeck, a 93-year-old retired pediatrician living in Fort Washington.

The discovery they made in 1951 and 1952 didn't come in time for Marc or Patricia Maurer. Nor did it come in time for RLF's most famous victim, Stevie Wonder, born prematurely in Michigan in 1950 as Steveland Judkins. Nor for 10,000 other babies born here and around the world who became blind from oxygen. But it did come in time for numberless preemies born in the last 50 years who can still see.

Survivors and Pioneers

Nobody knows the first infant to become blind from retrolental fibroplasia. But the first recorded in the annals of medicine is James Edgar Pew II.

Pew and his twin sister, Margaretta, were born on July 13, 1940, at the Boston Lying-In Hospital. They were seven weeks premature. Margaretta died in six hours. Her brother held on, thanks to oxygen.

"The child was examined at the age of ten minutes, at which time the respirations were gasping and irregular . . . the baby was immediately given oxygen. After about ten hours, his condition improved," the pediatrician in charge of the premature nursery, Stewart H. Clifford, wrote in the hospital chart, according to an account published in the Saturday Evening Post magazine in 1955.

The boy's father, George L. Pew, was extremely wealthy, a direct descendant of Joseph N. Pew, the founder of Sun Oil Company. (Today, the family name is best known for the foundation four of Joseph Pew's children endowed, the $4.1 billion Pew Charitable Trusts). Jimmy Pew received the best medical care money could buy. He spent two months in the hospital and got supplemental oxygen almost continuously.

When the boy was 7 months old, his parents and some visiting relatives became alarmed when he failed to track the movement of a cigarette lighter his father held in front of his face. (This anecdote, and many details of the following narrative, come from the magazine account by Steven M. Spencer and from a 1980 book, "Retrolental Fibroplasia: A Modern Parable," written by a pediatrician and historian named William A. Silverman.)